Hives, Angioedema, and Hashimoto’s Thyroiditis


Question

I have a female patient 38 yo dx with hashimoto's in late adolescense. She suffered from hyperthyroidism in her early childhood and was tx with PTU until the age of 16. She was dx with hashimoto's thyroiditis after the delivery of her first chold at 23 yrs and has been on Synthroid .125 since that time. She presents with severe urticaria and angioedema X 5 months now and has seen 4 other physicians including allergists, intensivists, internal med and endocrinology. Non with an answer to date.

Her labs: CBC, UA, Chem Panel - wnl. Her TSH 7.3, Thyroxine 11.6, T7 3.1, and T Uptake 26.7. Her thyroglubulin AB is 47, with a thyroid peroxidase of 710. Uric Acid 2.3, ASO <100, Rheumatoid factor <20, C-Reactive Protein <.5, sed rate 21, and a positive ANA with a titer of 1:1280. The only other positive on the panel was her thyroid microsomal AB at 367. Because they think her hives may be related to her hashimoto's, her endocrinologist has been trying to "put her thyroid asleep" by incrementally increasing her synthroid doses in an attempt to zero out her TSH. They have been working on this for 2months with what they hope to be the last increase started this week. She reports, however, that her symptoms have worsened since starting this process. Whether or not that is related to the change in dose of synthroid or simply coincidental I don't know. I am very interested in your thoughts on this.

Other lab work was performed to r/o hereditary angioedema Functional C1 esterase inhibitor > 100 and total C1 esterase inhibitor of 11. C3 Complement is 156 and C4 - 13. She has had a negative response to all allergy tests. Other labs done by a variety of people include a positive Circulating immune complex 0 25.1 and a neg IGE. Her LH, FSH and ACTH are also WNL.

She has had one of her hives Bx - pathology neg I am trying to find current case studies on the relationship of chronic urticaria and hashimoto's thyroiditis. I have found a few showing unremarkable results with increasing thyroxin doses, but heard of a case that a colleague in town tx by ablating a patients thyroid. Her hives were gone and she has remained hive free for almost 2 years now. I also read a case study from 1997 in Europe where a patient had a total thyroidectomy for the same reasons with immediate relief of urticaria and angioedema. I'm of course, very hesitent to recommend this drastic tx without more information. This patient is desparate, unable to work bcause of the debilitatin condition sheis in. Her current meds are synthroid .175, BCP's, Allegra 180mg tid, Tagamet 400mg tid, Zyrtec 10 mg bid, Atarax 50mg q4h prn. She has been on prednisone 60 mg for several weeks now with moderate relief, but can not wean off,due to the immediate return and the serious nature of these hives, covering 70 % of her body, angioedema affecting her eyes, lips, ears, larynx, throat and respiratory tract. She presents to the ER for respiratory Tx's and IV Solumedrol and/or epinephrine when things are escalating. Even on 60 mg of prednisone she is not hive free.

Any input you have would be greatly appreciated by all of us involved. Thank you very much. Please respond to my assistant at lwenham@patientshospital.com.

James Tate MD

First Response

- Dr Anthony Weetman will provide the official answer. However in the interim I will offer some comments. Certainly there is a statistical association between these two autoimmune diseases, but the relation is quite obscure. Suppressing the thyroid with excess T4 is an interesting approach, but hyperthyroidism might well exacerbate the hives and edema. I do not think there is any basis on which one can advise for thyroidectomy as a treatment. However as a trial in a terrible problem it is reasonable, and if done, I would suggest near total thyroidectomy followed by 131-I ablation.

Leslie J De Groot,MD

Second Response

BY DR ANTHONY WEETMAN -My understanding is that chronic urticaria has been reported to be more frequent in autoimmune thyroid disease and thyroid antibodies occur in up to 27% of patients with urticaria (J Allergy Clin Immunol 1989 84 66-71) . There is no specific feature of skin biopsy in patients with or without thyroid disease however and the urticaria does not improve with thyroxine (J Clin Immunol 2001 21 335-346).

I have no extensive personal experience but these findings had always made me think the association was simply one between 2 immunologically mediated diseases, and not a direct cause and effect as the correspondent is proposing. If it is simply an association, then thyroidectomy would be no more successful or logical than undertaking the same thing for Addison's disease, say, when it is associated with autoimmune hypothyroidism.

It certainly makes sense to get this patient's TSH normal on first principles but I doubt that further approaches to the thyroid will help and total thyroidectomy would be difficult in a patient with long standing hypothyroidism (subtotal thyroidectomy would have no theoretical benefit). Chronic urticaria is notoriously difficult to treat and the only other clue in this patient is the positive ANF. I am sure this must have been followed up but it would be worth repeatedly assessing for a collagen vascular disease.